title: Redox regulation of the tumor suppressor PTEN by glutaredoxin 5 and Ycp4.
abstract: Human PTEN (phosphatase and tensin homolog deleted on chromosome 10; a phosphatidylinositol 3-phosphatase) expressed in Saccharomyces cerevisiae was oxidized in a time- and H(2)O(2)-concentration-dependent manner. Oxidized hPTEN was reduced by cellular reductants as in human cells. The reduction rate of oxidized hPTEN was monitored in S. cerevisiae mutants in which the genes involved in redox homeostasis had been disrupted. Reduction of hPTEN was delayed in each of S. cerevisiae grx5Δ and ycp4Δ mutants. Expression of Grx5 and Ycp4 in each of the mutants rescued the reduction rate of oxidized hPTEN. Furthermore, an in vitro assay revealed that the human Grx5/GSH system efficiently catalyzed the reduction of oxidized hPTEN. These results suggest that the reduction of oxidized hPTEN is regulated by Grx5 and Ycp4.
authors.affiliation: Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Yujeong
authors.initials: Y
authors.lastname: Kim
authors.forename: Kee-Oh
authors.initials: KO
authors.lastname: Chay
authors.forename: Inyoung
authors.initials: I
authors.lastname: Kim
authors.forename: Yong Bhum
authors.initials: YB
authors.lastname: Song
authors.forename: Tae-Youl
authors.initials: TY
authors.lastname: Kim
authors.forename: Seong-Jeong
authors.initials: SJ
authors.lastname: Han
authors.forename: Younghee
authors.initials: Y
authors.lastname: Ahn
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Cho
authors.forename: Kwang-Lae
authors.initials: KL
authors.lastname: Hoe
authors.forename: Bong Whan
authors.initials: BW
authors.lastname: Ahn
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Huh
authors.forename: Seung-Rock
authors.initials: SR
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D005418:Flavodoxin / Q000378:metabolism*; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D005418:Flavodoxin; D054477:Glutaredoxins; D029701:Saccharomyces cerevisiae Proteins; C093705:YCP4 protein, S cerevisiae; D006861:Hydrogen Peroxide; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human